Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies (preprint)

Background Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle. Methods We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010-2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data we inferred transmission chains, estimated case detection and quantified the public health burden to evaluate these interventions. Results We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were highly cost-effective ($405 per death averted), their accessibility was limited and only dog vaccination interrupted transmission. A combined One Health approach rapidly eliminated rabies, was highly cost-effective ($1865 per death averted) and saved 20-120 families from rabid dog bites annually. Conclusions A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere. Funding Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa’s Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation (OPP49679) and whole-genome sequencing was partially supported at APHA by Defra grant SE0421.

Monitoring for outbreak associated excess mortality in an African city: Detection limits in Antananarivo, Madagascar (preprint)

Quantitative estimates of the impact of infectious disease outbreaks are required to develop measured policy responses. In many low- and middle-income countries, inadequate surveillance and incompleteness of death registration are important barriers. Here, we characterize how large an impact on mortality would have to be to be detectable using the uniquely detailed mortality notification data from the city of Antananarivo in Madagascar, with application to a recent measles outbreak. The weekly mortality rate of children during the 2018-2019 measles outbreak was 154% above the expected value at its peak, and the signal can be detected earlier in children than in the general population. This approach to detecting anomalies from expected baseline mortality allows us to delineate the prevalence of COVID-19 at which excess mortality would be detectable with the existing death notification system in the capital of Madagascar. Given current age-specific estimates of the COVID-19 fatality ratio and the age structure of the population in Antananarivo, we estimate that as few as 11 deaths per week in the 60-70 years age group (corresponding to an infection rate of approximately 1%) would detectably exceed the baseline. Data from 2020 will undergo necessary processing and quality control in the coming months. Our results provide a baseline for interpreting this information.

High variation expected in the pace and burden of SARS-CoV-2 outbreaks across sub-Saharan Africa (preprint)

A surprising feature of the SARS-CoV-2 pandemic to date is the low burdens reported in sub-Saharan Africa (SSA) countries relative to other global regions. Potential explanations (e.g., warmer environments [1], younger populations [2,3,4]) have yet to be framed within a comprehensive analysis accounting for factors that may offset the effects of climate and demography. Here, we synthesize factors hypothesized to shape the pace of this pandemic and its burden as it moves across SSA, encompassing demographic, comorbidity, climatic, healthcare and intervention capacity, and human mobility dimensions of risk. We find large scale diversity in probable drivers, such that outcomes are likely to be highly variable among SSA countries. While simulation shows that extensive climatic variation among SSA population centers has little effect on early outbreak trajectories, heterogeneity in connectivity is likely to play a large role in shaping the pace of viral spread. The prolonged, asynchronous outbreaks expected in weakly connected settings may result in extended stress to health systems. In addition, the observed variability in comorbidities and access to care will likely modulate the severity of infection: We show that even small shifts in the infection fatality ratio towards younger ages, which are likely in high risk settings, can eliminate the protective effect of younger populations. We highlight countries with elevated risk of slow pace, high burden outbreaks. Empirical data on the spatial extent of outbreaks within SSA countries, their patterns in severity over age, and the relationship between epidemic pace and health system disruptions are urgently needed to guide efforts to mitigate the high burden scenarios explored here.